1. Field of the Invention
The field of the invention relates to methods of modulating at least one trait in an animal. Such traits include increased life span, enhanced stress resistance and other traits associated with the stress response pathway. Also encompassed are transgenic animals produced by the disclosed methods.
2. Description of the Related Art
Stress response is a physiological phenomenon universal to all living species, which are constantly exposed to internal and external environmental challenges. Naturally the ability of an organism to react to various stress conditions plays a critical role in determining its chances of survival. One interesting example is the phenomenon of organismal longevity, i.e. long-term survival of an organism, which is closely associated stress resistance from species diverse as yeast and mammals (Guarente and Kenyon 2000; Kenyon 2001; Burgering and Kops 2002; Hekimi and Guarente 2003). Recent studies in model organisms, especially C. elegans, showed that the aging process is regulated by a conserved mechanism (Kenyon 2001). It has been well established that mutations in the insulin/IGF-1 signaling pathway in worm leads to extended life span, which is dependent on Daf16, a homolog of the vertebrate forkhead transcription factors (FOXOs) (Kenyon 2001). Among multiple processes perturbed in these long lived mutants, it is striking that stress resistance is the one that is most tightly coupled to longevity (Kenyon 2001). This raises the possibility that signaling pathways mediating stress response might play a direct role in life span extension, which is supported by recent findings on the stress-dependent regulation of FOXO by histone deacetylase SIRT1 (Brunet, Sweeney et al. 2004; Motta, Divecha et al. 2004).
Stress response pathways mediate cellular responses towards various physiological and environmental stress signals. Members of a family of stress activated kinases, including JNK and p38 MAP kinases, play a central role in stress response pathways (Chang and Karin 2001; Morrison and Davis 2003). Only a few studies, however, have directly examined and demonstrated a role for stress signaling proteins in the aging process (Wang, Bohmann et al. 2003). Indeed the molecular links that connect stress signaling to aging, and how signals from distinct pathways such as stress response pathway and insulin/IGF-1 pathway may be integrated to specify life span, are poorly understood. Filling such a gap by unifying these two major signaling routes will not only advance our understanding of the mechanisms of aging, but also provide insights into the signaling network implicated in various human diseases including cancer and diabetes. Thus there is a need for identification of the molecular links that connect the stress response to aging. Further, there is a need for methods of modulation of that molecular link to extend life span and increase stress tolerance of animals.